Oxidative stress and haemodialysis: role of inflammation and duration of dialysis treatment.

BACKGROUND: Oxidative stress has long been demonstrated in haemodialysis patients. However, the factors influencing their oxidative status have not been characterized extensively in these patients. Therefore, the present study was designed to investigate the influence of a large number of factors known to be associated with oxidative stress. METHODS: In the present cross-sectional study, we determined the plasma levels of lipid and protein oxidation markers in 31 non-smoking haemodialysis patients and 18 non-smoking healthy subjects, together with various components of the antioxidant system at the plasma and erythrocyte level. RESULTS: No influence of age, diabetes or iron overload on oxidative markers and plasma and erythrocyte antioxidant systems was detected in these haemodialysis patients. The lack of an association between iron overload and oxidative status may be related to the lower level of plasma ascorbate in haemodialysis patients, since ascorbate favours the generation of free iron from ferritin-bound iron. Interestingly, plasma C reactive protein (CRP) levels measured by highly sensitive CRP assay were correlated positively with plasma levels of thiobarbituric acid reactive substances (r=0.38, P<0.04) and negatively with plasma alpha-tocopherol levels (r=-0.46, P<0.01). Moreover, significant inverse correlations were observed between duration of dialysis treatment and plasma levels of alpha-tocopherol (r=-0.49, P<0.02) and ubiquinol (r=-0.40, P<0.05). CONCLUSIONS: Our results suggest that inflammatory status and duration of dialysis treatment are the most important factors relating to oxidative stress in haemodialysis patients.

Critical evaluation of plasma and LDL oxidant-trapping potential in hemodialysis patients.

BACKGROUND: We investigated whether the total peroxyl radical-trapping antioxidant potential (TRAP) assay, which has recently been proposed as a gauge of oxidative stress, could serve to evaluate plasma and low density lipoprotein (LDL) antioxidant state in hemodialysis (HD) patients. METHODS: TRAP was determined by the lag time of the chemiluminescence reaction induced by azo-initiator-catalyzed linoleic acid peroxidation in the plasma and corresponding LDL preparations of 23 HD patients and 22 healthy subjects. Antioxidant systems, including glutathione peroxidase (GSH-Px), ascorbate, vitamin E, and uric acid, oxidative stress markers including malondialdehyde (MDA), carbonyls, and advanced oxidation protein products (AOPP), and lipids, including cholesterol and triglycerides, were also determined in the plasma. RESULTS: Both plasma and LDL-TRAP were significantly increased in HD patients despite decreased GSH-Px and ascorbate and increased MDA, carbonyl, and AOPP plasma levels. Plasma TRAP values were closely related to both uric acid and AOPP levels, and LDL-TRAP values were related to triglycerides and AOPP levels. In vitro studies showed that: (a) plasma TRAP of control plasma increased regularly with supplementation of uric acid, although not reaching that of HD plasma with similar uric acid levels; (b) the addition of human serum albumin-AOPP also regularly increased control plasma TRAP, but was close to that of HD plasma with similar AOPP levels; and (c) LDL-TRAP was increased following LDL enrichment with triglycerides. CONCLUSION: Our study demonstrates that TRAP is not a relevant parameter for evaluating plasma or LDL antioxidant capacity in HD patients, due to the high plasma levels of uric acid, triglycerides and AOPP, which by themselves do not exert efficient antioxidant activity in vivo, but in vitro are able to scavenge the peroxyl radicals involved in the TRAP assay.

[Rapidly progressive glomerulonephritis in macroscopic periarteritis nodosa. 7 cases]. / Glomérulonéphrites rapidement progressives au cours de la périartérite noueuse macroscopique. Sept observations. Groupe de Traitement de la Périartérite Noueuse (Société Nationale Française de Médecine Interne).

Rapidly progressive glomerulonephritis (RPGN) is rarely associated with macroscopic polyarteritis nodosa (PAN), as seen in this series of 7 out of 235 patients. The clinical symptoms of PAN were as follows: myalgias 6; fever 1; arthralgias and mononeuropathy multiplex 5; cutaneous vasculitis 3; arterial hypertension 4, 3 of which were malignant. The mean proteinuria was 2.7 g/24 h; creatininemia 458 microM/l; microscopic hematuria was present in 4 of the 7 patients; only 1 patient was anuric. Markers of hepatitis B virus were absent in all cases. Arteriography revealed microaneurysms and renal infarcts in 6 patients and distal arterial stenosis in one. Renal biopsies from all 7 patients demonstrated extracapillary glomerulonephritis, which was associated with tubulointerstitial fibrosis in one. Necrotizing vasculitis lesions were associated in 5 cases. Immunofluorescence was positive in 5 cases. The association of RPGN and PAN exists and may be underestimated due to the lack of systematic angiographic examinations during RPGN and renal biopsies in PAN patients with renal involvement.

[Diagnostic and therapeutic management of ethylene glycol poisoning. Importance of crystalluria. Apropos of a case]. / Prise en charge diagnostique et thérapeutique de l'intoxication par l'éthylène glycol. Intérêt de la cristallurie. A propos d'une observation.

During the course of a case of ethylene glycol poisoning with ensuing oliguric renal failure despite early dialysis, we show the importance of early diagnosis of this intoxication in underlined. Characteristics of ethylene glycol poisoning are: metabolic acidosis with anion gap (without lactic acidosis or keto-acidosis) and high plasma osmolarity. Awaiting the result of blood and urinary toxic values, crystalluria, by typical needle monohydrate calcium oxalate crystals finding, evokes the diagnosis and permits to start a specific treatment. This treatment is based on: principles of intensive care, ethanol administration (or 4-methyl-pyrazole now available), also thiamine and pyridoxine administration and finally, dialysis therapy. We can hope, with early and intensive management of this poisoning, to prevent the renal failure, principal complication of ethylene glycol ingestion, which can lead to chronic renal failure. Therefore, crystalluria, an easy and specific diagnosis technic, is of great interest.

Pharmacokinetics of oxiracetam in patients with renal impairment after a 800 mg single oral dose.

The pharmacokinetics of oxiracetam in patients with renal impairment were investigated after administration of a 800 mg single oral dose of oxiracetam. The renal insufficiency was estimated on the basis of the creatinine clearance (CLcr) which ranged from 9 to 95 ml/min among the 20 patients. In plasma, the terminal elimination half-life (T1/2) ranged from 10.6 to 68.1 h, the highest T1/2 corresponding to the patients with a high degree of renal impairment. In urine, the amounts of oxiracetam excreted during the 48 h postdosing represented 8.3 to 82.6% of the dose. They were lower in patients with a high degree of renal impairment. The correlations between the total clearance of oxiracetam, the renal clearance, the terminal apparent elimination rate constant in plasma, and CLcr were estimated by linear regression analysis. The correlation coefficients were 0.916, 0.985 and 0.803 respectively. The apparent volume of distribution of the central compartment V(1) and the total volume of distribution at the steady-state V(SS) were not dependent on the degree of renal impairment. The mean values +/- SD were 25.9 +/- 13.0 litres and 48.3 +/- 21.5 litres respectively. Oxiracetam concentrations in plasma of patients were estimated for repeated administration of 800 mg of oxiracetam.(ABSTRACT TRUNCATED AT 250 WORDS)

[Epidemiology of primary glomerulonephritis in Picardie]. / Epidémiologie des glomérulopathies primitives en Picardie.

Between 1 January 1976 and 31 December 1986, primary glomerulonephritis was histologically diagnosed in 319 patients, living in a region of 675,000 inhabitants at the time of renal biopsy. The prevalence of primary glomerulopathy was 0.4/1000 inhabitants. The annual incidence was determined during two 5 year periods: period A (1976-1980) and period B (1981-1985): they were, respectively, 3.4 and 4.5 for 100,000 inhabitants. Berger's focal glomerulonephritis was the most common (30 p. 100) and its incidence was increasing. In contrast, membranoproliferative and acute glomerulonephritides were sharply decreased (almost disappeared), while membranous glomerulonephropathies and glomerulopathies with minimal glomerular lesions or proliferative forms with crescents increased. All primary glomerulonephritides were more prevalent in men and their frequencies increased with age. Our findings lead to the following conclusions: a) the low prevalence and incidence of primary glomerulopathies (3 times less than in other published studies) probably reflect the under medicalization of our region and the attractiveness of neighbouring metropolis, rather than a real decrease in the disease; b) the quasi- disappearance of acute and membranoproliferative glomerulonephropathies and the high incidence of IgA glomerulonephropathies suggest that their pathogenetic associations with infections sensitive to antibiotics are different; c) the increased frequency of membranous glomerulonephropathy and the glomerulopathy with minimal glomerular lesions in aged subjects is most likely due to their polymedication.

[Destructive spondylarthropathy with amyloid deposits in 3 patients on chronic hemodialysis]. / Spondylarthropathie destructrice avec dépôts amyloïdes chez 3 patients en hémodialyse chronique.

Destructive spondyloarthropathy is a recently described complication of chronic hemodialysis. Three patients presenting spondyloarthropathy with destructive discovertebral lesions of the cervical or lumbar sections of the spine underwent surgery due to neurologic complications: persistent radiculalgia (two cases), regressive tetraparesis (one case). Discal lesions were associated with dislocation of the posterior intervertebral articulations and slipping of vertebrae. These patients had been receiving chronic hemodialysis for more than ten years; two presented hyperparathyroidism and blood aluminum was markedly increased in all cases. Two patients had undergone surgery for bilateral carpal tunnel syndrome. Anatomopathological examination of surgical specimens demonstrated the presence of amyloid deposits in the intervertebral disc. This suggests that amyloidosis, which is frequently seen with carpal tunnel syndrome in patients receiving prolonged hemodialysis, also plays a role in the development of spondyloarthropathy.

The desferrioxamine test predicts bone aluminium burden induced by A1(OH)3 in uraemic patients but not mild histological osteomalacia.

Desferrioxamine (DFO), a chelating agent of aluminium was administered to 27 uraemic patients on chronic haemodialysis or haemofiltration with a minimal parenteral exposure to aluminium but taking various amounts of A1(OH)3 for about two years. All these patients had a double bone biopsy for measurement of their aluminium content and histomorphometric evaluation. Bone aluminium of our patients were 10 times greater than in our uraemic controls. Plasma aluminium increase (delta A1) induced by DFO correlated better than basal plasma aluminium with bone aluminium and cumulative dose of A1(OH)3 correlated with bone aluminium and delta A1 DFO. None of the patients had florid osteomalacia and only two had traces of aluminium staining. However 16 had mild mineralisation defect as demonstrated by low mineral appositional rate. The aluminium parameters were not different between the two groups of patients with or without mild mineralisation defect. It is concluded that the DFO test predicts bone aluminium but not mild histological osteomalacia in uraemic patients moderately aluminium over-loaded with phosphate binders.

Influence of biochemical and hormonal factors on the bone histomorphometric features of uraemic patients.

A multidimensional analysis was used to evaluate, the influence on bone histology of various biochemical and hormonal factors in 20 uraemic patients on chronic haemodialysis or haemofiltration. A positive relationship (p less than 0.1) was found between PTH and osteoclastic and osteoblastic surfaces but not with mineral apposition and bone formation rates. The mineral appositional rate which reflects the cellular activity of osteoblasts was positively related to D metabolites 25(OH)D3 and 1,25(OH)2D3 and to phosphate (p less than 0.1). Mineral appositional rate and bone formation rate were negatively related to bone aluminium (p less than 0.05). These data indicate that: 1) PTH simulates bone turnover but has no direct effect on the bone cellular activity of osteoblasts which is mainly dependent on D metabolites and phosphate; 2) mild aluminium overload not severe enough to cause osteomalacia decreases bone formation in uraemic patients. This study evaluates the role of various simultaneously measured biochemical and hormonal factors on bone histological parameters in uraemic patients.

Possible link between changes in plasma 24,25-dihydroxyvitamin D and healing of bone resorption in dialysis osteodystrophy.

Histomorphometric studies of bone biopsies were performed on 12 hemodialyzed patients before and after six months of treatment with 25-(OH) and 1 alpha-(OH) vitamin D3. Patients could be classified into three groups according to bone resorption: Group I with normal bone resorption; Group II with elevated initial bone resorption unresponsive to vitamin D treatment; group III with elevated initial bone resorption sensitive to vitamin D treatment. None of the patients had histological signs of osteomalacia. In Group I, plasma concentrations of 24,25-(OH)2D and the ratio of 24,25-(OH)2D to 25-(OH) D remained in the normal range throughout the study; in Group II these parameters were subnormal initially and did not increase above normal except in one case; in Group III, plasma concentrations of 24,25-(OH)2D were high before or at the beginning of vitamin D administration and normal at the time of the second biopsy and wide variations were observed in the ratio of 24,25-(OH)2D to 25-(OH)D. No difference was found between these last two groups with regard to the cumulative dose of vitamin D derivatives administered or the changes in plasma PTH, CT, calcium and phosphate. These observations suggest a specific regulation of plasma 24,25-(OH)2D concentrations in hemodialyzed patients and a possible link (independent of circulating PTH, CT, or phosphate) between this regulation and healing of bone resorption. However, no correlation was found between plasma 24,25-(OH)2D and either one of the simultaneously measured biochemical or histological parameters.

[Does 24,25 dihydroxycholecalciferol have a physiological and pathophysiological role?]. / Le 24,25 dihydroxycholécalciférol a-t-il un rôle physiologique et physiopathologique?

The authors review recent experimental and human data concerning the potential physiological and pathophysiological role of 24,25 (OH)2D3, the dihydroxylated metabolite of vitamin D which is synthetisized with preference over 1,25 (OH)2D3 in organisms that have been replenished with vitamin D. For the major known effects of vitamin D such as stimulation of intestinal absorption and bone resorption of calcium and phosphorus, 24,25 (OH)2D3 is less effective than the 1,25 (OH)2D3 metabolite and consequently of lesser physiological importance. Some recent in vitro experiments have shown, however, that 24,25 (OH)2D3 intervenes in the stimulation of proteoglycan synthesis, inhibition of PTH, vitamin A and heparin induced resorption, whereas 1,25 (OH)2D3 does not. Although there is controversy as to its direct inhibitory effect on secretion of PTH, it seems to act with 1,25 (OH)2D3 to prevent hyperplasia of parathyroids in vitamin D deficient chicken. From a pathophysiological point, the presence of 24,25 (OH)2D3 seems vital to allow normal bone formation and mineralisation and possibly to counteract excessive bone resorption.

[Evidence, in uremic man, of the role of beta 2 adrenergic receptors in the secretion of parathyroid hormone and calcitonin (author's transl)]. / Mise en évidence chez l'insuffisant rénal du rôle des récepteurs adrénergiques beta 2 dans la sécretion de l'hormone parathyroïdienne et de la calcitonine.

In order to determine the effect of beta-blocking agents on secretions of parathyroid hormone and calcitonin, 9 patients with renal failure were given single doses of propranolol (a blocker of the beta 1 and beta 2 receptors) or an equivalent amount of metoprolol (a beta 1 selective agent). Propranolol causes a decrease of plasma parathyroid hormone (p less than 0.02) as well as of calcitonin (p less than 0.05) whereas metoprolol has no effect on the plasma levels of these hormones. These findings suggest that parathyroid tissue and thyroid C cells have receptors that are exclusively of the beta 2 type which are modulating the secretion of parathyroid hormone and calcitonin.